Salmonella are facultative intracellular pathogens which cause significant diseases in humans and animals. These organisms cause several disease syndromes, including enteric (typhoid) fever, gastroenteritis, bacteremias and focal infections. Typhoid fever is a severe systemic illness which is mostly a problem in the developing world and in travelers. Non-typhoidal salmonella infections are increasing in the USA and are largely associated with contaminated food. Salmonellae infections are most severe in infants, the elderly, and in immunosuppressed individuals. This application proposes to study a set of virulence genes, termed Salmonella translocated effectors, that are translocated across the phagosome membrane into the eucaryotic cell cytoplasm by a type III secretion system encoded on Salmonella pathogenicity island II will be studied. This application proposes to further define these proteins, and to study in molecular detail their role in bacterial virulence. PUBLIC HEALTH RELEVANCE: Salmonellosis is the most common cause of bacterial diarrhea in the United States and typhoid fever remains an important global health problem for which antibiotic resistance is increasing. Studies of the molecular mechanisms of Salmonella virulence for humans and animals could lead to new vaccines and therapeutic strategies to prevent and treat Salmonellae infections.